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1.
Toxicol Res (Camb) ; 11(2): 367-373, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35510229

RESUMO

Drug-induced nephrotoxicity is a common problem in clinical medicine and the frequency of drug-related acute and chronic kidney dysfunction worldwide. One of them is anti-tuberculosis (TB) drugs that cause renal function impairment during TB treatment. Medicinal plants contain bioactive compounds that are capable for treating drug or toxin-induced renal disorders. The aim of the present study was to assess the protective effect of the ethanolic extract of Nigella sativa seeds (NS) against anti-TB drugs (ATDs) induced nephrotoxicity in Wistar albino rats. Rats were treated with ATDs for 12weeks (3 alternative days in a week). Supplementation with 125mg NS/kg, p.o. was administered to the experimental rats for 12weeks (3 alternative days in a week considering next day of ATDs treatment). The results demonstrated that NS treatment protected against renal damage induced by ATDs, as evidenced by the reduction in serum urea, creatinine, uric acid, urea nitrogen levels, pro-inflammatory markers (TNF-α and IL-6), whereas improvement in histological tubular and glomerular damage. In addition, NS enhanced the antioxidant enzyme activity (superoxide dismutase and catalase) and decreased the lipid peroxidation and glutathione level in the kidney. In conclusion, NS could reduce chronic nephritis in ATDs treated group through suppressing inflammation and oxidative stress. It suggests that NS can be used as supplementary preventive and protective drug against kidney injury during anti-TB treatment.

2.
Toxicol Res (Camb) ; 11(1): 215-225, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35237426

RESUMO

Acrylamide is a well-known neurotoxicant and carcinogen. Apart from industrial exposure, acrylamide is also found in different food products. The present study deals with in vivo experiment to test the protective effect of rutin against acrylamide induced toxicity in rats. The study was carried out on female rats with exposure of acrylamide at the dose of 38.27 mg/kg body weight, orally for 10 days followed by the therapy of rutin (05, 10, 20 and 40 mg/kg orally), for three consecutive days. All animals were sacrificed after 24 h of last treatment and various biochemical parameters in blood and tissue were investigated. Histopathology of liver, kidney and brain was also done. On administration of acrylamide for 10 days, neurotoxicity was observed in terms of decreased acetylcholinesterase activity and oxidative stress was observed in terms of increased lipid peroxidation, declined level of reduced glutathione, antioxidant enzymes (superoxide dismutase and catalase) in liver, kidney and brain. Acrylamide exposure increased the activities of serum transaminases, lipid profile, bilirubin, urea, uric acid and creatinine in serum indicating damage. Our experimental results conclude that rutin showed remarkable protection against oxidative DNA damage induced by acrylamide, which may be due to its antioxidant potential.

3.
Toxicol Res (Camb) ; 9(4): 406-412, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32905110

RESUMO

Present study was planned to investigate the ameliorative effect of silver nanoparticles (AgNPs) on acetaminophen-induced nephrotoxicity. Our results demonstrate that therapy of AgNPs at three different doses (50, 100 and 150 µg/kg once only) prevented the acetaminophen (2 g/kg once only) induced acute renal toxicity. AgNPs treated animals also show less intensity in the histological alterations in kidneys and corroborating the results of analysis of serum urea and creatinine. In addition, AgNPs therapy prevented the acetaminophen-induced oxidative stress, which was confirmed by the alleviated lipid peroxidation, enhanced renal reduced glutathione content and restored enzymatic activities of superoxide dismutase, catalase and adenosine triphosphatase in kidney. Thus, our results demonstrate a possible protective potential of AgNPs on renal toxicity induced by acetaminophen. This study will definitely lead to the development of therapeutic drug against nephrotoxicity, after further clinical and preclinical studies.

4.
Regul Toxicol Pharmacol ; 90: 36-41, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28827191

RESUMO

The present study was premeditated to demonstrate the hepatoprotective effect of silver nanoparticles (AgNPs). Rats were treated with three different doses of AgNPs (50, 100 and 150 µg/kg, p.o.) after Acetaminophen (APAP; 2 g/kg, p.o. once only) intoxication. Treatment with AgNPs recouped the levels of serum aspartate amino transaminase (AST), alanine amino transaminase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), bilirubin, triglyceride (TG) and cholesterol in dose dependent manner. Significant reduction in lipid peroxidation (LPO) and restoration of reduced glutathione (GSH) was found in liver in AgNPs treated animals. Alleviated activities of adenosine triphosphatase (ATPase), glucose-6- phosphatase (G6Pase) and antioxidant enzymes viz. superoxide dismutase (SOD) and catalase (CAT) due to APAP induced toxicity in liver were recovered by the treatment of AgNPs. Improvement in histoarchitecture of liver was also consistent with biochemical observations. The results revealed that AgNPs showed significant dose-dependent protection against APAP induced hepatocellular injury.


Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fígado/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Prata/uso terapêutico , Animais , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/citologia , Fígado/patologia , Testes de Função Hepática , Nanopartículas Metálicas/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Prata/farmacologia , Superóxido Dismutase
5.
Pharmacognosy Res ; 9(2): 208-214, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28539747

RESUMO

BACKGROUND: Justicia gendarussa Burm f. of family Acanthaceae is medicinally important herb used in the treatment of inflammatory disorders, asthma, hepatic injuries, pathogenic infection and also shows antiproliferative activity against various cancer cell lines. MATERIALS AND METHODS: Pharmacognostical evaluation (macro-microscopy, physicochemical analysis and preliminary phytochemical analysis), high-performance thin layer chromatography (HPTLC) fingerprinting and chemical profiling by gas chromatography-mass spectrometry (GCMS) of dried roots of J. gendarussa were done according to quality standard procedures. RESULTS: Microscopic analysis revealed the compact arrangement of cells in cork region and thin-walled cortex beneath epidermis. Parenchymatous cells with xylem vessel were observed in the roots of J. gendarussa. Physicochemical studies revealed loss on drying (10.474%), total ash (2.990%), acid-insoluble ash (0.099%), water-soluble ash (1.528%), alcohol-soluble extractive value (0.564%) and water-soluble extractive value (4.11%) of the raw drug. Preliminary phytochemical analysis of ethanolic extract of J. gendarussa showed the presence of alkaloid, steroid, flavonoid, phenol, carbohydrate, saponin and quinone. Rf, color of the spots and densitometric scan were recorded by HPTLC fingerprinting using toluene: ethyl acetate: formic acid (5.0:4.0:1.0). On photodocumentation, six spots were visualized under 254 nm, nine spots under 360 nm and six spots at 620 nm. Identification of components in ethanolic extract of J. gendarussa was done by GC-MS. GC-MS results in the presence of oleic acid, 9,12-octadecadienoic acid, 6,9,12-octadecatrienoic acid and estra-1, 3,5 (10)-trein-17-ß-ol in ethanolic extract of J. gendarussa. CONCLUSION: These specific identities will be useful in identification and authentication of the raw drug in dried form. SUMMARY: Transverse section and powder of dried roots of Justicia gendarussa were examined microscopically. Microscopic observations showed the presence of well-developed cork and cortex. Presence of xylem vessels and parenchymatic rays were observed in transverse section. Parenchymatous cell and sclereids with vessel elements were found in powder microscopyPhysicochemical studies revealed loss on drying (10.474%), total ash (2.990%), acid-insoluble ash (0.099%), water-soluble ash (1.528%), alcohol-soluble extract (0.564%) and water-soluble extract (4.11%)Preliminary phytochemical analysis of ethanolic extract of J. gendarussa showed the presence of alkaloid, steroid, flavonoid, phenol, carbohydrate, saponin and quinoneHigh-performance thin layer chromatography fingerprinting showed different peaks at different wavelengthChemical profiling of medicinal roots of J. gendarussa by gas chromatography. mass spectrometry revealed the presence of oleic acid, 9,12.octadecadienoic acid, 6,9,12-octadecatrienoic acid and estra-1,3,5 (10)-trein-17-ß-ol as bioactive compound. Abbreviations Used: TLC: Thin layer chromatography; HPTLC: High performance thin layer chromatography; GCMS: Gas chromatography-mass specrtometry; QSIMP: Quality standard of indian medicinal plant; LOD: Loss on drying; TA: Total ash; AIA: Acid insoluble ash; WSA: Water soluble ash; ASE: Alcohol soluble extractive; WSE: Water soluble extractive.

6.
Exp Toxicol Pathol ; 69(4): 231-240, 2017 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-28153389

RESUMO

Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2g/kg p.o. once only. After 24h of APAP intoxication, animals were treated with three different doses of AuNPs (50µg/kg, 100µg/kg, 150µg/kg) orally or silymarin at a dose of 50mg/kg p.o., once only. Animals of all the groups were sacrificed after 24h of last treatment. APAP administered group showed a significant rise in the AST, ALT, SALP, LDH, cholesterol, bilirubin, albumin, urea and creatinine in serum which indicated the hepato-renal damage. A significantly enhanced LPO and a depleted level of GSH were observed in APAP intoxicated rats. Declined activities of SOD and Catalase, after acetaminophen exposure indicated oxidative stress in liver and kidney. The activities of ATPase and glucose-6-Phosphatase were significantly inhibited after APAP administration. AuNPs treatment reversed all variables significantly towards normal level and was found nontoxic. Thus it is concluded that gold nanoparticles played a beneficial role in reducing acetaminophen induced toxicity and can be used in the development of drug against hepatic as well as renal diseases, after further preclinical and clinical studies.


Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Ouro/farmacologia , Rim/efeitos dos fármacos , Nanopartículas Metálicas/uso terapêutico , Animais , Doença Hepática Induzida por Substâncias e Drogas , Modelos Animais de Doenças , Feminino , Nefropatias/induzido quimicamente , Ratos , Ratos Wistar
7.
Biomed Pharmacother ; 86: 705-714, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28039850

RESUMO

Acrylamide (AA) is found in foods containing carbohydrates and proteins, where it is formed during the heating process. It is classified as neurotoxic and probably carcinogenic to humans. The present investigation was aimed to determine the lethal Dose (LD50) of AA and to evaluate the protective effects of quercetin (QE) against AA induced adverse effects in rats. For the determination of LD50, AA was administered orally at four different doses (46.4mg/kg, 100mg/kg, 215mg/kg and 464mg/kg) to experimental animals for seven days. After 7days LD50 of AA was determined using graphical method of Miller and Tainter. Then AA was administered at 1/3rd dose of LD50 (38.27mgkg-1 body weight; p.o. for 10 days) followed by the therapy of QE (5, 10, 20 and 40mg kg-1 orally), for 3 consecutive days for the determination of protective effect of QE against AA. The estimated LD50 of AA was 114.81mg/kg with 95% confidence interval. Exposure to AA 1/3rd dose of LD50 for 10days induced neurotoxicity which was confirmed by decreased acetylcholinesterase (AChE) activity. AA substantially increased lipid peroxidation (LPO), decreased the level of reduced glutathione (GSH) and antioxidant enzymes (SOD and CAT) in liver, kidney and brain. It also increased the activities of serum transaminases, urea, uric acid, creatinine, lipid profile, bilirubin in serum. Treatment with QE restored tissue and serological indices concomitantly towards normal levels. These results revealed that QE is able to significantly alleviate the toxicity induced by AA in rats.


Assuntos
Acrilamida/efeitos adversos , Síndromes Neurotóxicas/tratamento farmacológico , Quercetina/farmacologia , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Feminino , Glutationa/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Testes de Função Hepática/métodos , Síndromes Neurotóxicas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar
8.
J Environ Pathol Toxicol Oncol ; 35(1): 59-71, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27279584

RESUMO

Antituberculosis drug (ATD)-induced hepatotoxicity is a major impediment for the effective treatment of tuberculosis (TB). All first-line anti-TB medications have adverse effects that interrupt the successful completion of TB treatment. This investigation focuses on the evaluation of the protective role of Nigella sativa (NS) against liver injury caused by ATDs. Female rats were treated with ATDs for 8 weeks (3 d/wk) followed by NS for 8 weeks (3 d/wk). The antioxidant activity of NS was estimated with a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and by analyzing total phenolic contents. Qualitative characterization of active compounds of the plant was done by high-performance liquid chromotography (HPLC). ATD-induced adverse effects were associated with sharp elevation in levels of serum transaminases, albumin, cholesterol, urea, uric acid, creatinine, and blood urea nitrogen (BUN). ATDs significantly increased lipid peroxidation (LPO) and decreased enzyme activities (superoxide dismutase [SOD], catalase [CAT], adenosine triphosphatase [ATPase], and glucose-6-phosphatase [G6Pase]) in liver, indicating oxidative stress. Conjoint treatment with NS could reverse the serological biochemistry and inhibit oxidative stress by suppressing LPO and augmenting antioxidant enzyme activity toward that of the control. Histological studies support the above biochemical findings. Results indicate that NS exerts excellent hepatoprotective abilities and can be used as a supplement to improve patient adherence and reduce interruptions in treatment due to ATD-related liver injury.


Assuntos
Antioxidantes/metabolismo , Antituberculosos/efeitos adversos , Antituberculosos/antagonistas & inibidores , Fígado/efeitos dos fármacos , Nigella sativa/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Antituberculosos/toxicidade , Feminino , Testes de Função Hepática , Ratos , Ratos Wistar , Sementes/química
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